Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment: a patient-level meta-analysis from randomized controlled trials

Abstract

ObjectivesPatients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission.MethodsWe pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73 m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15–89 [CKD 2–4] and GFR<15 [CKD 5]). The main efficacy and safety endpoints were duration of antibiotic treatment and 30-day mortality.ResultsMean duration of antibiotic treatment was significantly shorter in PCT-guided (n=2,492) compared to control patients (n=2,510) (9.5–7.6 days; adjusted difference in days −2.01 [95% CI, −2.45 to −1.58]). CKD 5 patients had overall longer treatment durations, but a 2.5-day reduction in treatment duration was still found in patients receiving in PCT-guided care (11.3 vs. 8.6 days [95% CI −3.59 to −1.40]). There were 397 deaths in 2,492 PCT-group patients (15.9%) compared to 460 deaths in 2,510 control patients (18.3%) (adjusted odds ratio, 0.88 [95% CI 0.78 to 0.98)]. Effects of PCT-guidance on antibiotic treatment duration and mortality were similar in subgroups stratified by infection type and clinical setting (p interaction >0.05).ConclusionsThis individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates.

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials

“…To our knowledge, this is the first analysis addressing the effects of PCT guidance in patients within different age group. There is some overlap with previous secondary reports from the same database particularly regarding description of trials and methodology used for analysis [ 21 , 22 , 28 , 34 , 35 ]. The focus on age groups regarding effects of PCT use, however, is novel and has not been done in previous reports.…”

“…Still, it remains unclear whether data from these trials are also true for older patients who might have a different cytokine and biomarker response to infection compared to younger patients [ 26 , 27 ]. Older patients may have often impairment in kidney function, which may affect biomarker kinetics, but has not been shown to impact on PCT-guided stewardship efforts in a previous analysis [ 28 ]. Also, older patients have a less pronounced immune response to infection and important differences in regard to the adaptive and innate immunity have been well documented [ 26 ].…”

“…To address this significant drawback of earlier meta-analyses and to understand whether patient age would have an influence on the efficacy and safety of PCT protocols to guide antibiotic treatment, we did a secondary analysis of a previously published meta-analysis of individual patient data from 28 RCTs in patients with different types and severities of infection stratified in four different age groups. The main finding of the meta-analysis regarding effects of PCT use in patients with respiratory infections has been published previously [ 22 , 34 ], as well as other analyses looking specifically at specific subgroups of patients with sepsis [ 21 ] and patients with positive blood cultures [ 35 ], and associations of admission kidney function on PCT use [ 28 ]. We contacted the authors of 28 RCTs identified in the earlier meta-analysis [ 22 , 34 ] in order to obtain their original datasets.…”

Biomarker‐Guided Individualization of Antibiotic Therapy

“…However, extensive variation in observed biomarker dynamics remains a major challenge limiting further use of PCT as treatment response biomarker in patients with severe infections and sepsis. Such variability is associated with differences in underlying microbial etiologies, comorbidities, 82 and antibiotic treatments. All together, these factors make it more challenging to interpret and evaluate PCT biomarker time course data.…”

Concordance of Three Automated Procalcitonin Immunoassays at Medical Decision Points

“…Repeated PCT concentration assessment can be used to monitor the therapeutic response to guide medical decisions on early discontinuation of antibiotics and support personalized antibiotic management [ 2 , 3 ]. Multiple studies have shown that PCT-guided antibiotic initiation and discontinuation can shorten the duration of antibiotic treatment, which can in turn reduce the associated side effects and improve clinical outcomes [ 4 - 7 ]. Recently, two medical decision points have been suggested for PCT-guided antibiotic stewardship: 0.25 and 0.50 μg/L for non-intensive care unit (ICU) and ICU patients, respectively [ 2 ].…”